Hepatitis A

Question 1

To what family and genus does HAV belong?

Answer 1

HAV is a member of the genus Heparnavirus in the family Picornaviridae family.

Question 2

What is the geographical distribution of HAV?

Answer 2

Worldwide.

Question 3

What is the incidence of HAV infection?

Answer 3

Globally, an estimated 1.4 million cases occur each year.

Question 4

How is HAV transmitted?

Answer 4

HAV is usually transmitted by the fecal-oral route (either via person-to-person contact or consumption of contaminated food or water). Risk factors for HAV transmission include residence in or travel to areas to poor sanitation, household or sexual contact with another person with hepatitis A, homosexual activity in men, exposure to daycare centers, exposure to residential institutions, and illicit drug use. Bloodborne transmission can occur but is uncommon.

Question 5

How is HAV not transmitted?

Answer 5

Maternal-fetal transmission has not been described.

Question 6

Can HAV cause outbreaks?

Answer 6

Hepatitis A can occur sporadically or in an epidemic form.

Question 7

Write short notes on the pathogenesis of HAV infection.

Answer 7

Hepatic injury occurs as a result of the host immune response to hepatitis A virus (HAV). Viral replication occurs in the hepatocyte cytoplasm; hepatocellular damage and destruction of infected hepatocytes is mediated by human leukocyte antigen–restricted, HAV-specific CD8+ T lymphocytes and natural killer cells. Interferon-gamma appears to have a central role in promoting clearance of infected hepatocytes. An excessive host response (denoted by a marked reduction of circulation HAV RNA during acute infection) is associated with severe hepatitis.

Question 8

What’s the incubation period of HAV?

Answer 8

The incubation period of hepatitis A infection averages 28 days (range 15 to 50 days).

Question 9

How does HAV infection usually present?

Answer 9

Acute hepatitis A virus (HAV) infection in adults is usually a self-limited illness.

Question 10

What are the typical findings on history and examination in patients with HAV infection?

Answer 10

More than 70 percent of adults with HAV have symptomatic illness, which begins with abrupt onset of nausea, vomiting, anorexia, fever, malaise, and abdominal pain. Within a few days to a week, dark urine (bilirubinuria) appears; pale stools (lacking bilirubin pigment) may also be observed. These are followed by jaundice and pruritus (40 to 70 percent of cases). The early signs and symptoms usually diminish when jaundice appears, and jaundice typically peaks within two weeks.

Physical findings include fever, jaundice, scleral icterus, hepatomegaly (80 percent of cases), and abdominal pain. Less common findings include splenomegaly and extrahepatic manifestations such as skin rash and arthralgias.

Question 11

Discuss the lab findings typically found in patients with HAV infection.

Answer 11

Laboratory abnormalities include elevations of serum aminotransferases (often >1000 international units/dL), serum bilirubin (typically ≤10 mg/dL), and alkaline phosphatase (up to 400 U/L). The serum aminotransferase elevations precede the bilirubin elevation. Serum aminotransferases peak approximately one month after exposure to the virus and then decline by approximately 75 percent per week. The serum bilirubin concentration usually declines within two weeks of peak levels. Other laboratory abnormalities include elevations of acute-phase reactants and inflammatory markers.

Question 12

When are patients with HAV infectious?

Answer 12

Infected individuals are contagious during the incubation period and remain so for about a week after jaundice appears. HAV replicates in the liver and is shed in the stool in high concentrations from two to three weeks before to one week after onset of clinical illness.

Question 13

How do patients generally fare in typical HAV infection?

Answer 13

Full clinical and biochemical recovery is observed within two to three months in 85 percent of patients, and complete recovery is observed by six months in nearly all patients. HAV infection does not become chronic, and individuals cannot become reinfected after recovering from infection.

Question 14

Can HAV cause acute liver failure?

Answer 14

Yes.

Question 15

Write a short note on acute liver failure in HAV infection.

Answer 15

Fulminant hepatic failure develops in less than 1 percent of patients with hepatitis A; it occurs most commonly among patients with underlying liver disease, particularly chronic hepatitis C virus infection.

(and those >50 and those with other liver diseases, e.g. HBV)

Question 16

HAV infection can cause extra-hepatic manifestations. Say which patients are at greatest risk for these and which manifestations are the most common.

Answer 16

Extrahepatic manifestations occur most commonly in patients who have protracted illness such as relapsing or cholestatic hepatitis. The most common extrahepatic manifestations include evanescent rash and arthralgias (occurring in 10 to 15 percent of patients).

Question 17

What other conditions can be caused by HAV infection and what is the likely underlying mechanism?

Answer 17

Other conditions related to immune complex disease and vasculitis also occur, including:
●Leukocytoclastic vasculitis (most often apparent on the legs and buttocks; biopsy demonstrates anti-HAV immunoglobulin (Ig)M and complement in the blood vessel walls)
●Arthritis
●Glomerulonephritis
●Cryoglobulinemia
●Optic neuritis
●Transverse myelitis
●Toxic epidermal necrolysis
●Myocarditis
●Thrombocytopenia
●Aplastic anemia
●Red cell aplasia

Question 18

What are the complications of HAV infection?

Answer 18

Complications of acute hepatitis A infection include cholestatic hepatitis, relapsing hepatitis, and autoimmune hepatitis.

Question 19

Write short notes on cholestatic hepatitis secondary to HAV infection. Cover:

• Incidence
• Clinical course
• Imaging
• Treatment/Recovery

Answer 19

Prolonged cholestasis is characterized by a protracted period of jaundice (lasting >3 months); it occurs among fewer than 5 percent of patients with acute hepatitis A infection
.
The course of cholestatic hepatitis is usually characterized by marked jaundice, pruritus, fever, weight loss, diarrhea, and malaise. Laboratory findings include markedly elevated serum bilirubin (often >10 mg/dL) and alkaline phosphatase, modest elevation of serum aminotransferases, and elevated serum cholesterol. Peak bilirubin levels may be reached in the eighth week or later.

In general, cholestatic hepatitis resolves spontaneously with no sequelae; recognition is important to avoid unnecessary testing. Ultrasonography is appropriate to exclude biliary obstruction; cholangiography or liver biopsy are usually not necessary.

Treatment is usually supportive; there is no role for corticosteroids. Cholestyramine may be administered if pruritus is bothersome.

Question 20

Write short notes on relapsing hepatitis secondary to HAV infection. Cover;

• Incidence and duration
• Clinical course and extra-hepatic manifestations
• Multiple relapses
• Imaging
• Recovery

Answer 20

Up to 10 percent of patients experience a relapse of symptoms during the six months after acute illness. The duration of clinical relapse is generally less than 3 weeks, although biochemical relapse may last as long as 12 months

The clinical course usually consists of apparent clinical recovery after acute infection with near normalization of the serum aminotransferases, followed by biochemical (and, in some cases, clinical) relapse; clinical manifestations of relapse are often milder than the initial episode. HAV can be recovered from stool during relapse episodes, so such patients should be considered infectious.

Multiple relapses can occur. In one series including 297 adults with acute hepatitis A infection, relapse was observed in 13 percent of patients (of whom 22 percent had more than one relapse); approximately half of patients were asymptomatic during the relapses. Development of extrahepatic manifestations (such as arthritis, vasculitis, nephritis, and cryoglobulinemia) during relapse has been described.

In general, patients with relapsing hepatitis have complete recovery; recognition is important to avoid unnecessary testing. Ultrasonography is appropriate to exclude biliary obstruction in patients with significant jaundice; cholangiography or liver biopsy are usually not necessary.

Question 21

Comment on the relationship between HAV and autoimmune hepatitis.

Answer 21

Rarely, HAV infection may serve as a trigger for development of autoimmune hepatitis in susceptible individuals.

Question 22

How is the diagnosis of HAV infection established?

Answer 22

The diagnosis is established by detection of serum immunoglobulin (Ig)M anti-HAV antibodies.

Question 23

Describe the use of IgM anti-HAV antibodies in the diagnosis of HAV infection.

Answer 23

Serum IgM antibodies are detectable at the time of symptom onset, peak during the acute or early convalescent phase of the disease, and remain detectable for approximately three to six months. Among patients with relapsing hepatitis, serum IgM antibodies persist for the duration of this pattern of disease.

Detection of serum IgM antibodies in the absence of clinical symptoms may reflect prior hepatitis A infection with prolonged persistence of IgM, a false-positive result, or asymptomatic infection (which is more common in children <6 years of age than older children or adults).

Question 24

Comment on the presence of IgG anti-HAV antibodies in the serum.

Answer 24

Serum IgG antibodies appear early in the convalescent phase of the disease, remain detectable for decades, and are associated with lifelong protective immunity. Detection of anti-HAV IgG in the absence of anti-HAV IgM reflects past infection or vaccination rather than acute infection.

Question 25

Comment on the role of imaging in the diagnosis of HAV infection.

Answer 25

Imaging studies are generally not needed for diagnosis of HAV infection. Ultrasonography is appropriate to alternate diagnoses (such as biliary obstruction); cholangiography or liver biopsy are usually not necessary.

Question 26

Mention conditions in the differential diagnosis of HAV infection under the following headings:

• Other viruses
• Other infections
• Non-infectious conditions

Answer 26

Other viruses:
●Hepatitis B, C, D, and E 
●Epstein-Barr and cytomegalovirus 
●Yellow fever virus 
●Herpes simplex virus 
●Adenovirus
●HIV infection 

Other infections:
●Malaria 
●Leptospirosis 
●Syphilis 
●Q fever 

Non-infectious conditions:
●Drug-induced liver injury (DILI) 
●Budd-Chiari syndrome 
●Autoimmune hepatitis 
●Wilson disease

Question 27

What is the treatment of HAV infection?

Answer 27

Hepatitis A virus infection is usually self-limited, and treatment consists of supportive care. Medications that might cause liver damage or are metabolized by the liver should be used with caution.

Patients with fulminant hepatic failure require aggressive supportive therapy and should be transferred to a center capable of performing liver transplantation.

Question 28

Is the HAV vaccine given routinely in SA?

Answer 28

Not in State; it is in Private.

Question 29

Which unvaccinated medical patients should receive the vaccine?

Answer 29

●Men who have sex with men
●Illicit drug users (injection and noninjection)
●Individuals with chronic liver disease
●Individuals with clotting factor disorders

Question 30

Give a brief overview of the WHOs position on HAV vaccination.

Answer 30

Globally, the World Health Organization recommends immunization for children aged ≥1 year in places with intermediate endemicity on the basis of incidence of acute hepatitis A. In places of high endemicity, almost all persons are asymptomatically infected with HAV in childhood, which provides immunity against clinical infection; therefore, universal vaccination in these countries is not recommended.

Question 31

Is follow-up serologic testing required in immunocompetent patients?

Answer 31

Serologic testing following vaccination is not required in immunocompetent hosts given the high rate of vaccine response among adults and children. In general, completion of the vaccination may be presumed to confer lifelong protection.

Question 32

Which vaccines are available for HAV infection?

Answer 32

Inactivated HAV vaccine and live attenuated vaccine.

Question 33

What is the efficacy of the HAV vaccine?

Answer 33

The seroconversion rate (defined as an antibody concentration of >20 milli-international units [mIU]/mL measured by enzyme-linked immunosorbent assay [ELISA]) following primary vaccination series approximates 100 percent in healthy adults and children.

Question 34

In which subsets of patients might the immune response to the HAV vaccine be diminished?

Answer 34

In individuals with advanced liver disease, the serologic response to HAV vaccination may be diminished; if feasible, patients with liver disease should undergo vaccination before development of advanced disease.

In immunocompromised individuals, the serologic response to HAV vaccination may be diminished.

Question 35

Discuss the dosing and administration of the HAV vaccine. Cover:

• Dosing and administration
• Dosing in travellers
• Dosing interruptions

Answer 35

Immunization with single-antigen inactivated hepatitis A vaccine (HAVRIX or VAQTA) consists of two doses for children and adults.

For healthy individuals ≤40 years, the first dose of single-antigen hepatitis A vaccine should be given as soon as travel to areas with an intermediate or high rate of hepatitis A infection is considered and can be given at any time prior to departure.

For individuals >40 years, immunocompromised individuals, and persons with chronic liver disease or other chronic medical conditions with insufficient time to receive the full two-dose vaccination series before traveling, the first dose of vaccine should be administered together with a dose of immune globulin at a separate injection site.

If the immunization schedule is interrupted, the second dose can be given without restarting the series. It is good practice to use the same brand of vaccine to complete a course. If this is not possible, products for booster dose are interchangeable (eg, VAQTA can be used for booster dose following primary dose of HAVRIX and vice versa).

Question 36

List some common and some serious adverse effects reported with the HAV vaccine.

Answer 36

The most common adverse events are fever, injection-site reaction, rash, and headache. Serious adverse events (including Guillain-Barré syndrome, elevated liver biochemical tests, and immune thrombocytopenia) have been reported, although their relationship to vaccination is uncertain.

Question 37

Write short notes on the use of immune globulin in preventing HAV infection. Cover the following topics:

• Indications
• Duration of effect
• Dosing
• Reasons for limited usage

Answer 37

Pre-exposure protection against HAV via passive immunization with immune globulin is warranted for nonimmune individuals at risk for hepatitis A exposure in the following categories:
●Individuals >40 years, immunocompromised individuals, and persons with chronic liver disease or other chronic medical conditions with insufficient time to receive the full two-dose vaccination series before traveling; in such cases, the first dose of vaccine should be administered together with a dose of immune globulin at a separate injection site.
●Individuals who are allergic to the hepatitis A vaccine.
●Individuals <12 months of age.

Immune globulin provides protection against hepatitis A infection for up to three months and can decrease the incidence of HAV infection by more than 90 percent. Dosing consists of 0.02 mL/kg intramuscularly (for anticipated risk of exposure <3 months) or 0.06 mL/kg (for anticipated risk of exposure ≥3 months); administration must be repeated if the travel period exceeds 5 months.

Widespread use of immune globulin for hepatitis A prophylaxis is precluded by expense, injection site discomfort, need for repeat administration, and risk of bloodborne pathogen transmission (since the preparation is derived from pooled blood products).

Question 38

Discuss the indications for PEP in potential HAV infection

Answer 38

●Close personal contacts of an individual with laboratory-confirmed HAV infection:
•Household and sexual contacts
•Individuals who have shared illicit drugs
●Child care center contacts, in the setting of ≥1 case of hepatitis A among children or staff or ≥2 household cases of center attendees:
•For centers providing care to children in diapers: postexposure protection is warranted for all previously unvaccinated staff and attendees. In the setting of an outbreak (cases in ≥3 families), postexposure protection is also appropriate for household members of diaper-wearing children.
•For centers providing care to children who no longer wear diapers: postexposure protection is warranted for classroom contacts of the index patient (but not for children or staff in other classrooms).
●Food handlers:
•In establishments with a food handler diagnosed with hepatitis A, postexposure protection is warranted for other food handlers at the same establishment. Administration of postexposure protection to patrons is typically is not indicated; it is appropriate if the food handler had diarrhea or poor hygienic practices and directly handled uncooked foods or foods following cooking, and patrons can be identified and treated within two weeks of exposure.
•Postexposure prophylaxis is reasonable in settings in which repeated exposures to hepatitis A might have occurred, such as institutional cafeterias.

Question 39

What is the approach to PEP in HAV infection?

Answer 39

Individuals with recent HAV exposure who have not previously received HAV vaccine should receive postexposure prophylaxis with either a single dose of single-antigen HAV vaccine or immune globulin (0.02 mL/kg) as soon as possible, within two weeks of exposure:
●For healthy individuals aged 12 months to 40 years, single-antigen HAV vaccine should be administered. Vaccination is preferred over immune globulin since it induces active immunity and greater durability of protection, is easier to administer, and is more readily available than immune globulin.
●For individuals ≥41 years (particularly adults ≥75 years), immune globulin is preferred because of limited data regarding vaccine performance in this age group and because of the more severe manifestations of hepatitis A in older adults. Vaccine can be used if immune globulin cannot be obtained.
●For children <12 months, immunocompromised individuals, individuals with chronic liver disease, and individuals who are allergic to the vaccine, immune globulin (0.02 mL/kg) should be administered.

Question 40

Which intervention provides better protection: HAV vaccine or immune globulin?

Answer 40

They provide comparable protection.

Question 41

Can hepA/hepB combo vaccines be used for prophylaxis? What, if any, are the advantages?

Answer 41

The combination vaccine TWINRIX should not be used for postexposure prophylaxis.

Question 42

What hygiene practices may decrease the transmission of HAV?

Answer 42

Hygienic practices for prevention of hepatitis A virus (HAV) infection include:
●Handwashing (including after using the bathroom, changing diapers, and before preparing or eating foods).
●Avoiding tap water and raw foods in areas with poor sanitation.
●Heating foods appropriately (the virus can be inactivated by heating to >185°F [>85°C] for one minute). Cooked foods can transmit HAV if the temperature during food preparation is inadequate to kill the virus or if food is contaminated after cooking.
●Chlorine, iodine, and disinfecting solutions (household bleach 1:100 dilution) are effective for inactivation of HAV.